Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Combined Automated Annotation using Multiple IEA Methods
Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15
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Original cloning of human BACH2 as a B cell-specific transcription factor belonging to the CNC-bZIP family.
"The transcription factor Bach2, a member of the BTB-basic region leucine zipper (bZip) factor family, binds to a 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element and the related Maf-recognition element (MARE) by forming homodimers or heterodimers with Maf-related transcription factors."
Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1
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Demonstrated that BACH2 represses HMOX1 transcription. BCR-ABL/PI3K/S6K signaling phosphorylates BACH2 at Ser-521, promoting cytoplasmic accumulation and preventing nuclear translocation. S521A mutation leads to constitutive nuclear localization.
"We found that Bach2 is phosphorylated on S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this site to alanine leads to nuclear accumulation of the protein, indicating that this phosphorylation is important for its subcellular localization."
The structure of the Bach2 POZ-domain dimer reveals an intersubunit disulfide bond
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X-ray crystal structure of BACH2 BTB/POZ domain (residues 9-129) at 2.1A resolution reveals a homodimer with an intersubunit disulfide bond at Cys-20 that may regulate activity in oxidative stress responses.
"Here, the crystal structure of the human Bach2 POZ domain is reported at 2.1 Å resolution."
Networks of bZIP protein-protein interactions diversified over a billion years of evolution
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Systematic measurement of bZIP dimerization specificities across seven species including human. Identified BACH2 heterodimeric interactions with small MAF proteins (MAFG, MAFF, MAFK) and BATF3.
"We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs."
The Bach Family of Transcription Factors: A Comprehensive Review.
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Comprehensive review of Bach1 and Bach2 transcription factors. Describes BACH2 as repressing target gene expression by forming heterodimers with small Maf proteins. Reviews roles in B cell class-switch recombination, T cell homeostasis, oxidative stress-mediated apoptosis, and innate/adaptive immune responses.
"The transcription factors Bach1 and Bach2, which belong to a basic region-leucine zipper (bZip) family, repress target gene expression by forming heterodimers with small Maf proteins."
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation
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Identified BACH2 SUMOylation at Lys-382 and Lys-421 by mass spectrometry, suggesting SUMO-dependent regulation of BACH2 activity.
"Here we used an augmented K0-SUMO proteomics strategy to identify 40,765 SUMO acceptor sites and quantify their fractional contribution for 6,747 human proteins."
Impact of cytosine methylation on DNA binding specificities of human transcription factors
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Systematic SELEX analysis of 542 human TFs including BACH2. Demonstrated sequence-specific double-stranded DNA binding by BACH2 and characterized binding specificities including effects of CpG methylation.
"By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences."
Architecture of the human interactome defines protein communities and disease networks
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BioPlex 2.0 AP-MS study identifying BACH2 protein interactions including with FOSL2, BATF3, MAFF, and TULP3 among others.
"Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome"
BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency
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Characterized human BACH2 haploinsufficiency (BRIDA/IMD60) caused by heterozygous variants L24P and E788K. Patients showed intestinal inflammation, recurrent infections, impaired lymphocyte maturation, and decreased immunoglobulin production. Demonstrated BACH2 is a key regulator of adaptive immunity and Treg/B cell function.
"Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation."
A reference map of the human binary protein interactome
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HuRI reference interactome identifying binary protein interactions for BACH2 including canonical partners (MAFG, MAFK, MAFF) and many other proteins.
"Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
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BioPlex 3.0 interactome study confirming BACH2 interactions with small MAF proteins and other transcription factors.
"Here we present BioPlex 3.0, the most complete model of the human interactome to date, accompanied by a second interaction network acquired in HCT116 cells."
Multimodal cell maps as a foundation for structural and functional genomics
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Multimodal cell mapping confirming BACH2-MAFK interaction.
"Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells."